A case of acute and severe thrombocytopenia due to readministration of rifampicin

A 49-year-old-woman was diagnosed with tuberculosis of the left humerus. She had received treatment, including rifampicin, for tuberculosis 17 years previously. Treatment was begun with isoniazid, rifampicin, ethambutol, and pyrazinamide, but these were discontinued because of mild neutropenia and thrombocytopenia 2 weeks posttreatment. Rifampicin and ethambutol were readministered after a 4-day interruption; however, generalized purpura appeared several hours later. By the next day, her platelet count was reduced from 160 × 10³ to 3 × 10³/μl. The patient improved rapidly after platelet transfusion and steroid treatment. Readministration of drugs other than rifampicin did not induce thrombocytopenia; therefore, thrombocytopenia was likely due to rifampicin.     

Head circumference and body growth in autism spectrum disorders

Research has shown that there is a relationship between increased head circumference and autism spectrum disorders (ASD). This study examined this relationship during the first year of life in subjects with ASD. We compared 280 children with ASD and 609 controls. In the ASD-male group, increases were observed in head circumference from 3 to 12 months, in height from 3 to 9 months, and in body weight from 3 to 6 and 12 months. On the other hand, in the ASD-female group increases in head circumference, in body height, and in body weight were only observed at 3 months. After adjusting for height, weight, and age, only the head circumference in the male ASD group was significantly increased from 6 to 9 months after birth, reaching a peak at 6 months after birth. No difference was found in the female ASD group. Although body overgrowth in the ASD group also started early after birth, the increase in head circumference was more marked than that in body growth. The values of physical measurements in the first year may be useful, minimally invasive parameters for the early detection of autism in combination with observing the timing of certain behaviors such as smiling, eye contact, crawling, pointing, and joint attention.     

Endoplasmic reticulum stress inducers, but not imatinib, sensitize Philadelphia chromosome-positive leukemia cells to TRAIL-mediated apoptosis

Philadelphia-chromosome (Ph1)-positive leukemia cells frequently express death receptors DR4/DR5 for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and show high TRAIL-sensitivity. It has been reported that imatinib damaged cardiomyocytes by triggering endoplasmic reticulum (ER) stress and that ER stress inducers intensified TRAIL-sensitivity of some cancer cells by upregulating DR4/DR5 expression. In fact, ER stress inducers enhanced TRAIL-sensitivity of Ph1-positive leukemia cells by upregulating DR4/DR5 expression. In contrast, imatinib did not induce ER stress responses and unexpectedly downregulated DR4/DR5 expression, indicating that sensitization of Ph1-positive leukemia cells to TRAIL-mediated cellular immunity by imatinib through upregulation of DR4/DR5 expression is unlikely.     

Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice

In humans, digoxin is mainly eliminated through the kidneys unchanged, and renal clearance represents approximately 70% of the total clearance. In this study, we used the mouse models to examine digoxin pharmacokinetics in polyuria induced by diabetes mellitus and lithium carbonate (Li(2)CO(3)) administration, including mechanistic evaluation of the contribution of glomerular filtration, tubular secretion, and tubular reabsorption. After digoxin administration to streptozotocin (STZ)-induced diabetic mice, digoxin CL/F increased to approximately 2.2 times that in normal mice. After treatment with Li(2)CO(3) (0.2%) for 10 days, the CL/F increased approximately 1.1 times for normal mice and 1.6 times for STZ mice. Creatinine clearance (CLcr) and the renal mRNA expression levels of mdr1a did not differ significantly between the normal, STZ, and Li(2)CO(3)-treated mice. The urine volume of STZ mice was approximately 26?mL/day, 22 times that of normal mice. The urine volume of Li(2)CO(3)-treated mice increased approximately 7.3 times for normal mice and 2.3 times for STZ mice. These results suggest that the therapeutic effect of digoxin may be significantly reduced in the presence of polyuria either induced by diabetes mellitus or manifested as an adverse effect of Li(2)CO(3) in diabetic patients, along with increased urine volume.     

Relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype

Paternal uniparental disomy 14 (UPD(14)pat) results in a unique constellation of clinical features, and a similar phenotypic constellation is also caused by microdeletions involving the DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and/or the MEG3-DMR and by epimutations (hypermethylations) affecting the DMRs. However, relative frequency of such underlying genetic causes remains to be clarified, as well as that of underlying mechanisms of UPD(14)pat, that is, trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and post-fertilization mitotic error (PE). To examine this matter, we sequentially performed methylation analysis, microsatellite analysis, fluorescence in situ hybridization, and array-based comparative genomic hybridization in 26 patients with UPD(14)pat-like phenotype. Consequently, we identified UPD(14)pat in 17 patients (65.4%), microdeletions of different patterns in 5 patients (19.2%), and epimutations in 4 patients (15.4%). Furthermore, UPD(14)pat was found to be generated through TR or GC in 5 patients (29.4%), MR or PE in 11 patients (64.7%), and PE in 1 patient (5.9%). Advanced maternal age at childbirth (≥35 years) was predominantly observed in the MR/PE subtype. The results imply that the relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype is different from that of other imprinting disorders, and that advanced maternal age at childbirth as a predisposing factor for the generation of nullisomic oocytes through non-disjunction at meiosis 1 may be involved in the development of MR-mediated UPD(14)pat.     

Artepillin C, as a PPARγ ligand, enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells

The nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ plays an important role in adipocyte differentiation. Its ligands, including thiazolidinediones, improve insulin sensitivity in type 2 diabetes. We investigated the effects of artepillin C, an ingredient of Baccharis dracunculifolia, on adipogenesis and glucose uptake using 3T3-L1 cells. In PPARγ ligand-binding assays, artepillin C exhibited binding affinity toward PPARγ. Artepillin C dose-dependently enhanced adipocyte differentiation of 3T3-L1 cells. As a result of the artepillin C-induced adipocyte differentiation, the gene expression of PPARγ and its target genes, such as aP2, adiponectin and glucose transporter (GLUT) 4, was increased. These increases were abolished by cotreatment with GW9662, a PPARγ antagonist. In mature 3T3-L1 adipocytes, artepillin C significantly enhanced the basal and insulin-stimulated glucose uptake. These effects were decreased by cotreatment with a PI3K inhibitor. Although artepillin C had no effects on the insulin signaling cascade, artepillin C enhanced the expression and plasma membrane translocation of GLUT1 and GLUT4 in mature adipocytes. In conclusion, these findings suggest that artepillin C promotes adipocyte differentiation and glucose uptake in part by direct binding to PPARγ, which could be the basis of the pharmacological benefits of green propolis intake in reducing the risk of type 2 diabetes.     

Miniaturized biocompatible cardiopulmonary bypass for the Fontan procedure

Purpose  

Postoperative inflammatory response and perioperative systemic edema are the risks of failed Fontan circulation. We evaluated the efficiency of the miniaturized, poly-2-methoxyethylacrylate (PMEA)-coated cardiopulmonary bypass (CPB) circuit, which we devised in 2003, in the Fontan circulation.     

The effectiveness of high-flow regional cerebral perfusion in Norwood stage I palliation

Objective: Regional cerebral perfusion (RCP) has been shown to provide cerebral circulatory support during Norwood procedure. In our institution, high-flow RCP (HFRCP) from the right innominate artery has been induced to keep sufficient cerebral and somatic oxygen delivery via collateral vessels. We studied the effectiveness of HFRCP to regional cerebral and somatic tissue oxygenation in Norwood stage I palliation. Methods: Seventeen patients, who underwent the Norwood procedure, were separated into two groups: group C (n = 6) using low-flow RCP and group H (n = 11) using HFRCP (mean flow: 54 vs 92 ml kg⁻¹ min⁻¹, P < 0.0001). The mean duration of RCP was 64 ± 10 min (range, 49–86 min) under the moderate hypothermia. Chlorpromazine (3.0 mg kg⁻¹) was given to group H patients before and during RCP to increase RCP flow. The mean radial arterial pressure was kept <50 mmHg during RCP. To clarify the effectiveness of HFRCP for cerebral and somatic tissue oxygenation, cerebral regional oxygen saturation (rSO₂) and systemic venous oxygenation (SvO₂) during RCP were compared between the two groups. Changes in the lactate level before and after RCP, and changes in the blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and creatinine kinase (CK) levels before and after surgery, were also compared between the groups. Results: Mean rSO₂ was 82.9 ± 9.0% in group H and 65.9 ± 10.7% in group C (P < 0.05). Mean SvO₂ during RCP was 98.2 ± 4.3% in group H and 85.4 ± 9.7% in group C (P < 0.01). During RCP, lactate concentration significantly increased in group C compared with that in group H (P < 0.001). After surgery, the LDH and CK levels significantly increased in group C compared with that in group H (P < 0.05). Conclusions: Our study revealed that HFRCP preserved sufficient cerebral and somatic tissue oxygenation during the Norwood procedure. The reduction of vascular resistance of collateral vessels increased both cerebral and somatic blood flow, resulting in improved tissue oxygen delivery.     

A case of a 6-year-old girl with anti-neutrophil cytoplasmic autoantibody-negative pauci-immune crescentic glomerulonephritis

A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.